Unraveling the Therapeutic Potential of CEP-7055: Targeting VEGF Receptors for Antiangiogenic and Antitumor Effects in Oncology

CEP-7055 is a synthetic compound derived from CEP-5214, which is known for its ability to inhibit various vascular endothelial growth factor receptors (VEGF-R). This compound has shown effectiveness in suppressing tumor angiogenesis, a process necessary for tumor growth and spread. CEP-5214 has been tested and found to have low IC50 values against different VEGF-R kinases, indicating its strong inhibitory potential. It has also been shown to inhibit VEGF-induced autophosphorylation in human endothelial cells with high potency and to prevent microvessel growth in both ex vivo and in vitro assays without causing cytotoxicity.

In animal studies, both CEP-7055 and CEP-5214 have demonstrated the ability to inhibit VEGF-R2/FLK-1 phosphorylation in lung tissues upon single-dose administration. Furthermore, CEP-7055 has shown significant reductions in neovascularization, granuloma formation, and VEGF-induced plasma extravasation when administered orally to mice. Chronic administration of CEP-7055 has resulted in substantial inhibition of tumor growth in various types of murine and human tumor xenografts, including melanomas, glioblastomas, lung carcinomas, pancreatic carcinomas, colon carcinomas, breast carcinomas, and angiosarcomas. The compound has also shown significant antitumor efficacy against prostate carcinomas and renal carcinomas in mice, reducing metastatic scores and pulmonary metastases.

The antitumor effects of CEP-7055 have been associated with increased tumor apoptosis and decreased microvessel density within the tumors. Importantly, the efficacy of CEP-7055 was found to be independent of the initial tumor volume and reversible upon treatment withdrawal. In preclinical studies, CEP-7055 was well tolerated with no apparent toxicity or significant morbidity even after prolonged administration. The compound has advanced to Phase I clinical trials for cancer patients, indicating its potential as a therapeutic agent in oncology.